Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

Background and purpose Previous studies,mostly focusing on the European population,have reported polygenic risk scores(PRSs)might achieve risk stratification of stroke.We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.Methods Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set(n=22191)and a population-based testing set(n=72150).Four previously developed PRSs were included,and new PRSs for stroke and its subtypes were developed.The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set.Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes(ischaemic stroke(IS),intracerebral haemorrhage(ICH)and subarachnoid haemorrhage(SAH)).Results In the testing set,during 872919 person-years of follow-up,8514 incident stroke events were documented.The PRSs of any stroke(AS)and IS were both positively associated with risks of AS,IS and ICH(p<0.05).The HR for per SD increment(HR_(SD))of PRSAS was 1.10(95%CI 1.07 to 1.12),1.10(95%CI 1.07 to 1.12)and 1.13(95%CI 1.07 to 1.20)for AS,IS and ICH,respectively.The corresponding HR_(SD) of PRS_(IS) was 1.08(95%CI 1.06 to 1.11),1.08(95%CI 1.06 to 1.11)and 1.09(95%CI 1.03 to 1.15).PRS_(ICH) was positively associated with the risk of ICH(HR_(SD)=1.07,95%CI 1.01 to 1.14).PRSS_(AH) was not associated with risks of stroke and its subtypes.The addition of current PRSs offered little to no improvement in stroke risk prediction and risk stratification.Conclusions In this Chinese population,the association strengths of current PRSs with risks of stroke and its subtypes were moderate,suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asian population.

Multimorbidity patterns and association with mortality in 0.5 million Chinese adults

Background:Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population.We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.Methods:We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years.Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline.Multimorbidity patterns were identified using hierarchical cluster analysis.Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.Results:Overall,15.8%of participants had multimorbidity.The prevalence of multimorbidity increased with age and was higher in urban than rural participants.Four multimorbidity patterns were identified,including cardiometabolic multimorbidity(diabetes,coronary heart disease,stroke,and hypertension),respiratory multimorbidity(tuberculosis,asthma,and chronic obstructive pulmonary disease),gastrointestinal and hepatorenal multimorbidity(gallstone disease,chronic kidney disease,cirrhosis,peptic ulcer,and cancer),and mental and arthritis multimorbidity(neurasthenia,psychiatric disorder,and rheumatoid arthritis).During a median of 10.8 years of follow-up,49,371 deaths occurred.Compared with participants without multimorbidity,cardiometabolic multimorbidity(hazard ratios[HR]=2.20,95%confidence intervals[CI]:2.14-2.26)and respiratory multimorbidity(HR=2.13,95%CI:1.97-2.31)demonstrated relatively higher risks of mortality,followed by gastrointestinal and hepatorenal multimorbidity(HR=1.33,95%CI:1.22-1.46).The mortality risk increased by 36%(HR=1.36,95%CI:1.35-1.37)with every additional disease.Conclusion:Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.